The total synthesis of deoxybouvardin and bouvardin (NSC 259968), ususual bicyclic hexapeptides with confirmed antitumor propeties, are detailed. Antitumor and antimicrobial structure-activity relationships of deoxybouvardin and bouvardin, including the evaluation of partial structures, are to be pursued. The approach to the preparation of deoxybouvardin and bouvardin relies on the development and implementation of approaches to the preparation of the unusual diaryl ether linked cyclic 14-membered dipeptide ( a meta- and paracyclophane dipeptide) evidently required for antitumor activity, and its incorporation into the bicyclic hexapeptide structure constituting the structural framework of the naturally occurring materials.